Diethyl Ether → Ethyl 6-Aminonicotinate

HRID 1789802Notes

Reaction equation

HRID 1789802 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:10])=[O:9])=[CH:4][N:3]=1.O=S(Cl)Cl.[CH2:15](OCC)[CH3:16].[OH-].[Na+]>C(O)C.CO.C1COCC1>[CH2:15]([O:9][C:8](=[O:10])[C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=1)[CH3:16]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 184966-Aminonicotinic acidHCID 24386Thionyl Chloride3×

Product 1

HCID 235927Ethyl 6-AminonicotinateYield 97%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-5-pyridinecarboxylic acid (25.0 g, 181 mmol) was suspended in ethanol (190 mL) and SOCl2 (15 mL, 206 mmol) was added. The mixture was refluxed for 10 hs and more SOCl2 (16 mL) was added. After 3 days with reflux (and more SOCl2 (10 mL) added each day), the reaction mixture was cooled to room temperature and diethyl ether was added. After 24 h at −20° C. the mixture was filtered. The crude salt was dissolved in methanol (214 mL) and a solution of NaOH (40.0 g, 23.5 mmol) in methanol (90 mL) was added. The reaction mixture was stirred for 1 h and THF (270 mL) was added. The reaction mixture was filtered through a plug of silica (THF/MeOH) and concentrated under reduced pressure to give 6-amino-nicotinic acid ethyl ester (36.2 g, 97%).

Workup

  1. additionwas added
  2. additionadded each day), the reaction mixture
  3. filtrationAfter 24 h at −20° C. the mixture was filtered
  4. dissolutionThe crude salt was dissolved in methanol (214 mL)
  5. filtrationThe reaction mixture was filtered through a plug of silica (THF/MeOH)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a2acfb645bed42be8eb04a3e474dcc98
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

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